Mesothelioma Clinical Trials

This study will determine the dose of the experimental
anticancer drug SS1(dsFv)-PE38 that can be given safely to
patients. It will also look at how the body handles the drug,
its side effects, and its effect on the tumor. SS1(dsFv)-PE38
will be tried in patients with solid tumors that have an
antigen called mesothelin. This is a protein that is normally
produced by cells lining body cavities, but has also been
found on several types of cancer cells. The drug
SS1(dsFv)-PE38 is composed of SS1, a protein that binds
tightly to mesothelin, and PE38, parts of the Pseudomonas
exotoxin (PE) protein, which can kill human cells if it gains
entry to them. SS1(dsFv)-PE38 is designed to attach to
mesothelin on the cancer cells and allow entry of the PE38,
which will then destroy the cells.

Patients 18 years of age and older with malignant
mesothelioma or cancer of the head, neck, lung, cervix or
ovaries may be eligible for this study. Candidates will have a
medical history, physical examination, blood and urine tests,
electrocardiogram (EKG) and chest X-ray, and tumor evaluation
with computerized tomography (CT) scans or other imaging
tests.

Participants will receive SS1(dsFv)-PE38 intravenously
(through a vein) for 10 consecutive days. Weight and vital
signs (temperature, heart and breathing rate and blood
pressure) will be recorded and blood tests will be done during
and after the treatment to look for side effects. Physical
exams and blood and urine tests will be done to evaluate side
effects weekly for two weeks, or more often if side effects
occur. Depending on side effects, treatments may be repeated
every 4 weeks for a maximum of four treatments. Physical
examinations and blood and urine tests will be repeated with
each treatment, and X-rays or CT scans will be done four weeks
after each treatment to measure the effect of treatment on the
tumor. An EKG will be repeated after three courses of
treatment, or sooner if treatment is stopped. After the final
treatment, follow-up visits will be scheduled at 3-month
intervals.

Condition

Treatment or
Intervention

MesotheliomaOvarian
NeoplasmSquamous Cell
Neoplasm

Drug: SS1
(dsFv)-PE38

This is a Phase I test

In Phase I clinical trials,
researchers test a new drug or treatment in a small
group of people (20-80) for the first time to evaluate its safety, determine
a safe dosage range, and identify side effects.

Study Type: InterventionalStudy
Design: Treatment

Official Title: Phase I Study
of SS1 (dsFv)-PE38 (SS1P) Anti-Mesothelin Immunotoxin in Advanced Malignancies:
Continuous Infusion For 10 Days

Further Study Details:

This is a Phase I study of the SS1 (dsFv)-PE38 recombinant
toxin in patients with selected advanced solid tumors which
express mesothelin. SS1 (dsFv)-PE38 recombinant immunotoxin is
composed of disulfide-stabilized variable region of
anti-mesothelin monoclonal antibody, conjoined to PE38- the
translocation and enzymatic domains of Pseudomonas exotoxin A.

Safety of SS1 (dsFv)-PE38 was documented in mice at 400
micrograms/kilograms/day by continuous i.p. infusion x 7 days
(total dose 2.8 mg/kg) and in monkeys at a dose of 100
micrograms/kilograms/day by i.v. bolus x 10 days (total 1.0
mg/kg). In this study, SS1 (dsFv)-PE38 will be administered by
continuous i.v. infusion for 10 days; Phase I starting dose
will be 8 micrograms/kilograms/day (total 0.08 mg/kg).
Patients with tumor response or stabilization may be retreated
to a maximum of four courses.

The primary objective of this study is to determine the
dose-limiting toxicities and pharmacokinetics of SS1
(dsFv)-PE38 when given by continuous infusion in cancer
patients. Secondary objectives include a preliminary response
assessment, to evaluate anti-tumor activity in selected
measurable malignancies for which mesothelin expression has
been determined, as well as immunologic and pharmacokinetic
objectives.

Genders Eligible for Study: Both

Criteria

INCLUSION CRITERIA:Histopathologic
diagnosis of one of the following malignancies:Malignant
mesothelioma;Ovarian carcinoma, all epithelial
histologies, including primary peritoneal and fallopian tube
carcinoma. This includes tumors involving ovary and also
bowel, which could possibly have originated from bowel, such
as appendiceal carcinoma.Pancreatic cancer;Squamous
cell cancer of the lung;Squamous cell cancer of the head
and neck;Squamous cell cancer of the cervix.Recurrent
unresectable disease in patients who have received or are
unwilling to receive standard therapies or anticancer
therapies that are expected to prolong survival and improved
quality of life.Tumor (initial or recurrent; greater than
or equal to 30% of tumor cells) must be positive (at least 1+)
for mesothelin by immunohistochemistry.No concurrent
anti-tumor treatment. At least 4 weeks since any prior
anti-tumor therapy, with recovery from side effects and at
least one week since any hematopoetic growth factor
therapy.Measurable or evaluable tumor documented within 4
weeks prior to study entry.Age greater than or equal to 18
years.Life expectancy greater than or equal to 12
weeks.Performance Status (ECOG) 0-2.Adequate organ
function, including:ANC greater than or equal to
1,000/mm(3); Plts greater than or equal to
75,000/mm(3);Creatinine less than or equal to
Institutional Upper Limit Normal (ULN) or Creatinine less than
or equal to 2.0 mg/dL if 24-hour urinary Creatinine Clearance
is greater than or equal to 50 cc/min, Ca (2+) and total
Bilirubin less than or equal to upper limit normal (ULN); AST
(SGOT) and ALT (SGPT) less than or equal to 2.5 x
ULN;Albumin greater than or equal to 3.0 gm/dL;S0(2)
greater than 92% (room air).Sign informed consent, in
accordance with institutional criteria.EXCLUSION
CRITERIA:Patient may not have any of the following:Any
known CNS or spinal cord involvement by tumor.Detectable
antibody to SS1 (dsFv)-PE38.Concurrent antitumor
therapy.Cardiovascular condition NY Heart Association
Grade II-IV, or any clinically-significant pericardial
effusion.An infection requiring parenteral antibiotics,
HIV infection, or seropositivity for Hepatitis B and Hepatitis
C.Be pregnant or nursing. Females of child-bearing
potential must use an effective method of
contraception.